Engineering microbial systems
The vast majority of plant-derived natural products (also known as ‘specialised metabolites’) have complex structures and stereochemistry that are beyond the reach of chemical synthesis. Furthermore, most of these compounds cannot be extracted in a sustainable and economical manner from their source plants due to low yield, difficulties in cultivation, or because the source material is a rare or endangered species. In addition there is a growing demand for green, environmentally friendly and sustainable means of producing high-value chemicals across a wide range of industrial sectors. We are working on the production of high-value chemicals from plants through expression of biosynthetic enzymes in microbial hosts, focusing on the largest class of plant-derived natural products – the terpenes. Terpenes range from small flavour and fragrance compounds to complex triterpenoids and steroids, and have numerous potential applications across the pharmaceutical, home and personal care, agriculture, food and beverage sectors. Advances in our understanding of the genes and enzymes required for biosynthesis coupled with affordable commercial DNA synthesis and developments in DNA assembly technologies now offer unprecedented opportunities to use synthetic biology approaches to harness plant metabolic diversity and generate novel molecules.
We have developed an innovative, versatile technology for enzymatically assembling and dynamically rearranging DNA modules. This platform enables rapid assembly of multiple standardized DNA modules into large assemblies such as metabolic pathways and to exchange individual parts of assemblies (e.g., regulatory elements) to allow variation and optimization. We will use this platform in combination with the in silico design and large scale DNA synthesis capability at the Edinburgh Genome Foundry to enable synthesis of complex constructs for multi-step metabolic pathways and to tune expression levels of individual genes in the pathway to appropriate levels aiding flux through the pathway and enhancing product formation.
- With our collaborators Prof Anne Osbourn (John Innes Centre) and Prof Jay Keasling (JBEI and University of Berkeley, CA) we are engineering pathways for the production of diverse, valuable plant derived triterpenes in Saccharomyces cerevisiae.
- We are engineering in vivo biosensors for natural products and their variants and use these sensors in high throughput screens allowing dynamic optimization of metabolic pathways.
- In collaboration with Prof Osbourn and Unilever we are working to produce plant derived triterpenoidal or steroidal surfactants, saponins, in yeast for commercial exploitation at the required scale, structure specificity & cost, for home & personal care applications.
